JP5136938B2 - ベンゾイミダゾール単位を含む三環式ｎ−ヘテロアリール−カルボキサミド誘導体、それらの調製方法およびそれらの治療上の使用 - Google Patents

ベンゾイミダゾール単位を含む三環式ｎ−ヘテロアリール−カルボキサミド誘導体、それらの調製方法およびそれらの治療上の使用 Download PDF

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Publication number: JP5136938B2
Authority: JP; Japan
Prior art keywords: alkyl; group; compound; cycloalkyl; alkylene
Prior art date: 2006-02-03
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

JP2008552848A

Other languages

English (en)

Japanese (ja)

Other versions

JP2009525313A (ja

Inventor

デユボワ，ローラン

エバノ，ヤニク

エバン，リユク

ジル，カトリンヌ

マランダ，アンドレ

マクニク，ダビツド

ラコトアリゾア，ナタリー

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Sanofi SA

Original Assignee

Sanofi SA

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2006-02-03

Filing date

2007-02-01

Publication date

2013-02-06

2007-02-01 Application filed by Sanofi SA filed Critical Sanofi SA

2009-07-09 Publication of JP2009525313A publication Critical patent/JP2009525313A/ja

2013-02-06 Application granted granted Critical

2013-02-06 Publication of JP5136938B2 publication Critical patent/JP5136938B2/ja

Status Expired - Fee Related legal-status Critical Current

2027-02-01 Anticipated expiration legal-status Critical

Links

238000000034 method Methods 0.000 title claims description 55
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 title claims description 24
238000002360 preparation method Methods 0.000 title claims description 16
230000001225 therapeutic effect Effects 0.000 title description 4
229940053202 antiepileptics carboxamide derivative Drugs 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims description 296
125000003118 aryl group Chemical group 0.000 claims description 66
-1 C 1 -C 6 - alkyloxy Chemical group 0.000 claims description 65
150000001412 amines Chemical class 0.000 claims description 64
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 45
229910052757 nitrogen Inorganic materials 0.000 claims description 43
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 42
125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 41
125000001072 heteroaryl group Chemical group 0.000 claims description 39
125000004433 nitrogen atom Chemical group N* 0.000 claims description 35
125000005843 halogen group Chemical group 0.000 claims description 34
125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 claims description 33
125000004429 atom Chemical group 0.000 claims description 25
230000008569 process Effects 0.000 claims description 22
239000002253 acid Substances 0.000 claims description 21
150000003839 salts Chemical class 0.000 claims description 20
229910052717 sulfur Inorganic materials 0.000 claims description 18
239000012453 solvate Substances 0.000 claims description 17
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 16
239000002904 solvent Substances 0.000 claims description 16
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 15
229910052799 carbon Inorganic materials 0.000 claims description 15
125000004093 cyano group Chemical group *C#N 0.000 claims description 15
125000004104 aryloxy group Chemical group 0.000 claims description 14
125000005553 heteroaryloxy group Chemical group 0.000 claims description 14
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
229910052760 oxygen Inorganic materials 0.000 claims description 14
125000005842 heteroatom Chemical group 0.000 claims description 13
125000001424 substituent group Chemical group 0.000 claims description 12
238000011282 treatment Methods 0.000 claims description 12
230000002265 prevention Effects 0.000 claims description 11
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 10
208000002193 Pain Diseases 0.000 claims description 10
125000004432 carbon atom Chemical group C* 0.000 claims description 10
125000002947 alkylene group Chemical group 0.000 claims description 9
125000005110 aryl thio group Chemical group 0.000 claims description 9
125000000623 heterocyclic group Chemical group 0.000 claims description 9
230000036407 pain Effects 0.000 claims description 9
229910052698 phosphorus Inorganic materials 0.000 claims description 9
229910052727 yttrium Inorganic materials 0.000 claims description 9
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 8
239000003814 drug Substances 0.000 claims description 8
125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 8
102000005962 receptors Human genes 0.000 claims description 8
108020003175 receptors Proteins 0.000 claims description 8
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 7
JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 claims description 7
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
125000004043 oxo group Chemical group O=* 0.000 claims description 6
238000010992 reflux Methods 0.000 claims description 6
125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 6
125000004434 sulfur atom Chemical group 0.000 claims description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 6
102000003563 TRPV Human genes 0.000 claims description 5
108060008564 TRPV Proteins 0.000 claims description 5
230000009471 action Effects 0.000 claims description 5
125000002619 bicyclic group Chemical group 0.000 claims description 5
208000035475 disorder Diseases 0.000 claims description 5
125000005368 heteroarylthio group Chemical group 0.000 claims description 5
125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 4
239000007822 coupling agent Substances 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
125000000169 tricyclic heterocycle group Chemical group 0.000 claims description 4
FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical group C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 claims description 3
206010061218 Inflammation Diseases 0.000 claims description 3
150000007513 acids Chemical class 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 3
150000001408 amides Chemical class 0.000 claims description 3
XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 claims description 3
HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 3
ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical group C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 claims description 3
231100000013 eye irritation Toxicity 0.000 claims description 3
150000004677 hydrates Chemical class 0.000 claims description 3
230000004054 inflammatory process Effects 0.000 claims description 3
125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 3
125000005000 thioaryl group Chemical group 0.000 claims description 3
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 3
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 2
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
208000018522 Gastrointestinal disease Diseases 0.000 claims description 2
208000007514 Herpes zoster Diseases 0.000 claims description 2
XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 claims description 2
150000001204 N-oxides Chemical class 0.000 claims description 2
208000003251 Pruritus Diseases 0.000 claims description 2
201000004681 Psoriasis Diseases 0.000 claims description 2
125000005529 alkyleneoxy group Chemical group 0.000 claims description 2
150000003951 lactams Chemical class 0.000 claims description 2
208000030159 metabolic disease Diseases 0.000 claims description 2
231100000017 mucous membrane irritation Toxicity 0.000 claims description 2
201000006417 multiple sclerosis Diseases 0.000 claims description 2
239000001301 oxygen Substances 0.000 claims description 2
230000001575 pathological effect Effects 0.000 claims description 2
208000023504 respiratory system disease Diseases 0.000 claims description 2
231100000475 skin irritation Toxicity 0.000 claims description 2
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 1
238000002560 therapeutic procedure Methods 0.000 claims 1
208000014001 urinary system disease Diseases 0.000 claims 1
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 186
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 138
239000000203 mixture Substances 0.000 description 89
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 84
239000000047 product Substances 0.000 description 81
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 73
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
239000000243 solution Substances 0.000 description 58
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 54
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 51
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 40
238000003756 stirring Methods 0.000 description 37
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
239000007787 solid Substances 0.000 description 36
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 34
239000000377 silicon dioxide Substances 0.000 description 34
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 33
238000004440 column chromatography Methods 0.000 description 32
239000011541 reaction mixture Substances 0.000 description 31
239000012074 organic phase Substances 0.000 description 30
YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 28
239000007864 aqueous solution Substances 0.000 description 26
239000002585 base Substances 0.000 description 26
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 24
238000010828 elution Methods 0.000 description 24
239000000725 suspension Substances 0.000 description 22
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 21
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
229910052786 argon Inorganic materials 0.000 description 20
238000002844 melting Methods 0.000 description 20
230000008018 melting Effects 0.000 description 20
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 19
238000001914 filtration Methods 0.000 description 19
229910052938 sodium sulfate Inorganic materials 0.000 description 18
235000011152 sodium sulphate Nutrition 0.000 description 18
229910052763 palladium Inorganic materials 0.000 description 17
239000011780 sodium chloride Substances 0.000 description 17
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 16
238000001035 drying Methods 0.000 description 15
239000008346 aqueous phase Substances 0.000 description 14
229960002504 capsaicin Drugs 0.000 description 14
235000017663 capsaicin Nutrition 0.000 description 14
239000002198 insoluble material Substances 0.000 description 13
229920006395 saturated elastomer Polymers 0.000 description 13
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 12
229910052943 magnesium sulfate Inorganic materials 0.000 description 12
235000019341 magnesium sulphate Nutrition 0.000 description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
239000003480 eluent Substances 0.000 description 11
ONXVHKXADDPGSJ-UHFFFAOYSA-N 2,3-dihydro-1h-pyrrolo[1,2-a]benzimidazol-6-amine Chemical compound NC1=CC=C2N(CCC3)C3=NC2=C1 ONXVHKXADDPGSJ-UHFFFAOYSA-N 0.000 description 10
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 10
239000003054 catalyst Substances 0.000 description 10
239000003153 chemical reaction reagent Substances 0.000 description 10
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
KJVBJICWGQIMOZ-UHFFFAOYSA-N 2-fluoro-5-nitroaniline Chemical compound NC1=CC([N+]([O-])=O)=CC=C1F KJVBJICWGQIMOZ-UHFFFAOYSA-N 0.000 description 9
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
210000004027 cell Anatomy 0.000 description 9
238000006243 chemical reaction Methods 0.000 description 9
239000000543 intermediate Substances 0.000 description 9
RPBNVHBOPVXZFO-UHFFFAOYSA-N pyrazino[1,2-a]benzimidazol-7-amine Chemical compound C1=NC=CN2C3=CC(N)=CC=C3N=C21 RPBNVHBOPVXZFO-UHFFFAOYSA-N 0.000 description 9
BUXCYCBXQZXFKZ-UHFFFAOYSA-N pyrimido[1,2-a]benzimidazol-7-amine Chemical compound N1=CC=CN2C3=CC(N)=CC=C3N=C21 BUXCYCBXQZXFKZ-UHFFFAOYSA-N 0.000 description 9
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
230000015572 biosynthetic process Effects 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
239000012047 saturated solution Substances 0.000 description 8
239000012312 sodium hydride Substances 0.000 description 8
229910000104 sodium hydride Inorganic materials 0.000 description 8
238000003786 synthesis reaction Methods 0.000 description 8
241001465754 Metazoa Species 0.000 description 7
125000000217 alkyl group Chemical group 0.000 description 7
150000001721 carbon Chemical group 0.000 description 7
238000009903 catalytic hydrogenation reaction Methods 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
239000002244 precipitate Substances 0.000 description 7
BFFFMKMPLHVQSA-UHFFFAOYSA-N 1-methyl-7-nitro-2,4-dihydro-1h-imidazo[1,2-a]benzimidazole Chemical compound C1=C([N+]([O-])=O)C=C2N3C(C)CNC3=NC2=C1 BFFFMKMPLHVQSA-UHFFFAOYSA-N 0.000 description 6
HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
150000002391 heterocyclic compounds Chemical class 0.000 description 6
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 6
239000000843 powder Substances 0.000 description 6
210000003594 spinal ganglia Anatomy 0.000 description 6
CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 6
230000006399 behavior Effects 0.000 description 5
239000000872 buffer Substances 0.000 description 5
ICXSNKYNSFFOFS-UHFFFAOYSA-N ethyl 5-fluoro-1-[(3-fluorophenyl)methyl]indole-2-carboxylate Chemical compound CCOC(=O)C1=CC2=CC(F)=CC=C2N1CC1=CC=CC(F)=C1 ICXSNKYNSFFOFS-UHFFFAOYSA-N 0.000 description 5
230000005764 inhibitory process Effects 0.000 description 5
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
239000002243 precursor Substances 0.000 description 5
239000000126 substance Substances 0.000 description 5
ZLAFVSXXGDPVKG-UHFFFAOYSA-N 1,2,3,4-tetrahydropyrido[1,2-a]benzimidazol-7-amine Chemical compound C1CCCC2=NC3=CC(N)=CC=C3N21 ZLAFVSXXGDPVKG-UHFFFAOYSA-N 0.000 description 4
LOQLBMYYBHCMJJ-UHFFFAOYSA-N 1-chloro-2-iodo-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C(I)=C1 LOQLBMYYBHCMJJ-UHFFFAOYSA-N 0.000 description 4
IWWDWKKCXOJTGC-UHFFFAOYSA-N 4-methyl-7-nitro-2,3,4,10-tetrahydropyrimido[1,2-a]benzimidazole Chemical compound C1=C([N+]([O-])=O)C=C2N3C(C)CCNC3=NC2=C1 IWWDWKKCXOJTGC-UHFFFAOYSA-N 0.000 description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
229910000024 caesium carbonate Inorganic materials 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
229910052801 chlorine Inorganic materials 0.000 description 4
238000005859 coupling reaction Methods 0.000 description 4
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
230000000694 effects Effects 0.000 description 4
FMQODFCMDNPTRF-UHFFFAOYSA-N ethyl 5-fluoro-1-(pyridin-4-ylmethyl)indole-2-carboxylate Chemical compound CCOC(=O)C1=CC2=CC(F)=CC=C2N1CC1=CC=NC=C1 FMQODFCMDNPTRF-UHFFFAOYSA-N 0.000 description 4
VIKOQTQMWBKMNA-UHFFFAOYSA-N ethyl 5-fluoro-1h-indole-2-carboxylate Chemical compound FC1=CC=C2NC(C(=O)OCC)=CC2=C1 VIKOQTQMWBKMNA-UHFFFAOYSA-N 0.000 description 4
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 4
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 4
239000001257 hydrogen Substances 0.000 description 4
229910052739 hydrogen Inorganic materials 0.000 description 4
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 4
239000002609 medium Substances 0.000 description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
239000003921 oil Substances 0.000 description 4
235000019198 oils Nutrition 0.000 description 4
LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 4
229910000027 potassium carbonate Inorganic materials 0.000 description 4
235000011181 potassium carbonates Nutrition 0.000 description 4
125000006239 protecting group Chemical group 0.000 description 4
230000009467 reduction Effects 0.000 description 4
230000004044 response Effects 0.000 description 4
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
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Classifications

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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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- C—CHEMISTRY; METALLURGY
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JP2008552848A 2006-02-03 2007-02-01 ベンゾイミダゾール単位を含む三環式ｎ−ヘテロアリール−カルボキサミド誘導体、それらの調製方法およびそれらの治療上の使用 Expired - Fee Related JP5136938B2 (ja)

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FR06/01007		2006-02-03
FR0601007A FR2897061B1 (fr)	2006-02-03	2006-02-03	Derives de n-heteroaryl-carboxamides tricycliques contenant un motif benzimidazole, leur preparation et leur application en therapeutique.
PCT/FR2007/000183 WO2007088277A1 (fr)	2006-02-03	2007-02-01	Dérivés de ν-heteroaryl-carboxamides tricycliques contenant un motif benzimidazole, leur préparation et leur application en thérapeutique

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US (2)	US8143248B2 (es)
EP (1)	EP1987010B1 (es)
JP (1)	JP5136938B2 (es)
KR (1)	KR20080090495A (es)
CN (1)	CN101379041B (es)
AR (1)	AR059279A1 (es)
AT (1)	ATE463484T1 (es)
AU (1)	AU2007211399B2 (es)
BR (1)	BRPI0710480A2 (es)
CA (1)	CA2637333C (es)
CY (1)	CY1110168T1 (es)
DE (1)	DE602007005779D1 (es)
DK (1)	DK1987010T3 (es)
DO (1)	DOP2007000022A (es)
EA (1)	EA014450B1 (es)
ES (1)	ES2344087T3 (es)
FR (1)	FR2897061B1 (es)
HK (1)	HK1129670A1 (es)
HR (1)	HRP20100327T1 (es)
IL (1)	IL192648A (es)
JO (1)	JO2602B1 (es)
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NO (1)	NO20083520L (es)
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PL (1)	PL1987010T3 (es)
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SI (1)	SI1987010T1 (es)
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UY (1)	UY30130A1 (es)
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Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2888848B1 (fr) *	2005-07-22	2007-09-28	Sanofi Aventis Sa	Derives de n-(arylalkyl)-1h-pyrrrolopyridine-2-carboxamides, leur preparation et leur application en therapeutique
FR2911605B1 (fr)	2007-01-19	2009-04-17	Sanofi Aventis Sa	Derives de pyrrolopyridine-2-carbowamides, leur preparation et leur application en therapeutique
FR2911604B1 (fr) *	2007-01-19	2009-04-17	Sanofi Aventis Sa	Derives de n-(heteroaryl-1h-indole-2-carboxamides, leur preparation et leur application en therapeutique
FR2919610B1 (fr) *	2007-08-02	2009-10-16	Sanofi Aventis Sa	Derives de n-heteroaryl-carboxamides tricycliques,leur preparation et leur application en therapeutique
FR2926556B1 (fr) *	2008-01-22	2010-02-19	Sanofi Aventis	Derives de carboxamides n-azabicycliques, leur preparation et leur application en therapeutique
FR2926555B1 (fr) *	2008-01-22	2010-02-19	Sanofi Aventis	Derives bicycliques de carboxamides azabicycliques, leur preparation et leur application en therapeutique
FR2926554B1 (fr)	2008-01-22	2010-03-12	Sanofi Aventis	Derives de carboxamides azabicycliques, leur preparation et leur application en therapeutique
FR2926553B1 (fr) *	2008-01-23	2010-02-19	Sanofi Aventis	Derives d'indole-2-carboxamides et d'azaindole-2- carboxamides substitues par un groupe silanyle, leur preparation et leur application en therapeutique
WO2009108551A2 (en) *	2008-02-25	2009-09-03	H. Lundbeck A/S	Heteroaryl amide analogues
WO2010005528A2 (en) *	2008-06-30	2010-01-14	Ironwood Pharmaceuticals Incorporated	Pyrrolopyridine carboxylic acid derivatives
AU2009308687A1 (en) *	2008-11-03	2010-05-06	Chemocentryx, Inc.	Compounds for the treatment of osteoporosis and cancers
BRPI1008020A2 (pt)	2009-02-11	2016-03-15	Sunovion Pharmaceuticals Inc	antagonistas e agonistas inversos h3 da histamina e métodos de uso dos mesmos
US20120172350A1 (en) *	2009-09-11	2012-07-05	Sunovion Pharmaceuticals Inc.	Histamine h3 inverse agonists and antagonists and methods of use thereof
CA2797762A1 (en) *	2010-04-27	2011-11-03	Astellas Pharma Inc.	Imidazo[1,2-a]pyridine derivative
AU2013232069B2 (en)	2012-03-16	2017-07-13	Vitae Pharmaceuticals, Inc.	Liver X receptor modulators
EP2825541B1 (en) *	2012-03-16	2016-06-22	Vitae Pharmaceuticals, Inc.	Liver x receptor modulators
RU2659779C2 (ru)	2012-06-18	2018-07-04	Дарт Нейросайенс (Кайман) Лтд	Замещенные соединения тиофен- и фуран-конденсированного азолопиримидин-5-(6н)-она
CN106573899B (zh)	2014-08-04	2021-04-06	纽韦卢森公司	用于治疗炎性、代谢性、肿瘤性和自身免疫性疾病的任选稠合的、经杂环基取代的嘧啶衍生物
US10513694B2 (en)	2015-06-25	2019-12-24	Promega Corporation	Thienopyrrole compounds and uses thereof
JP7187449B2 (ja) *	2016-09-30	2022-12-12	エピザイム，インコーポレイティド	Ｅｈｍｔ２阻害剤としての置換された融合二環式または三環式複素環化合物
JP7161475B2 (ja)	2016-12-28	2022-10-26	プロメガコーポレイション	官能化ｎａｎｏｌｕｃ阻害剤
US11672800B2 (en)	2017-04-21	2023-06-13	Epizyme, Inc.	Combination therapies with EHMT2 inhibitors
CN109761974B (zh) *	2019-01-21	2021-05-14	河南大学	1,2,3,4-四氢-9H-吡啶并[3,4-b]吲哚类TRPV1拮抗剂及其应用
AU2020405446A1 (en)	2019-12-20	2022-05-26	Nuevolution A/S	Compounds active towards nuclear receptors
AU2021245397A1 (en)	2020-03-31	2022-10-20	Nuevolution A/S	Compounds active towards nuclear receptors
MX2022012259A (es)	2020-03-31	2022-12-08	Nuevolution As	Compuestos activos frente a receptores nucleares.
CN114276354B (zh) *	2022-01-07	2023-06-02	中山大学	1-氨基苯并[4,5]咪唑并[1,2-a]吡嗪-3-甲酰胺类化合物及其制备和应用
CN114539265B (zh) *	2022-03-02	2023-07-21	中山大学	靶向a2a的苯并咪唑并吡嗪-3-甲酰胺及其肿瘤免疫功能

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2003037274A2 (en) *	2001-11-01	2003-05-08	Icagen, Inc.	Pyrazole-amides and-sulfonamides
AU2003281044A1 (en) *	2002-07-11	2004-02-02	Takeda Pharmaceutical Company Limited	Pyrrolopyridine derivative and use thereof
WO2004069792A2 (en) *	2003-02-03	2004-08-19	Janssen Pharmaceutica N.V.	Quinoline-derived amide modulators of vanilloid vr1 receptor
GB0322016D0 (en) *	2003-09-19	2003-10-22	Merck Sharp & Dohme	New compounds
US7544803B2 (en) *	2004-01-23	2009-06-09	Amgen Inc.	Vanilloid receptor ligands and their use in treatments
DE102004021716A1 (de) *	2004-04-30	2005-12-01	Grünenthal GmbH	Substituierte Imidazo[1,2-a]pyridin-Verbindungen und Arzneimittel enthaltend substituierte Imidazo[1,2-a]pyridin-Verbindungen
EP2314585B1 (en) *	2004-07-15	2012-09-12	Japan Tobacco, Inc.	Condensed benzamide compounds as inhibitors of vanilloid receptor subtype 1 (VR1) activity

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Publication number	Publication date
PE20071325A1 (es)	2008-02-21
CY1110168T1 (el)	2015-01-14
DE602007005779D1 (de)	2010-05-20
AU2007211399A1 (en)	2007-08-09
ATE463484T1 (de)	2010-04-15
PT1987010E (pt)	2010-06-25
NZ569669A (en)	2011-05-27
BRPI0710480A2 (pt)	2012-08-14
NO20083520L (no)	2008-09-11
ES2344087T3 (es)	2010-08-17
MA30229B1 (fr)	2009-02-02
UY30130A1 (es)	2007-09-28
RS51366B (en)	2011-02-28
FR2897061A1 (fr)	2007-08-10
ZA200806139B (en)	2010-05-26
CN101379041B (zh)	2012-08-29
KR20080090495A (ko)	2008-10-08
HRP20100327T1 (hr)	2010-08-31
PL1987010T3 (pl)	2010-09-30
US20090042873A1 (en)	2009-02-12
AR059279A1 (es)	2008-03-19
IL192648A0 (en)	2009-02-11
DK1987010T3 (da)	2010-08-02
TW200738726A (en)	2007-10-16
EA200870226A1 (ru)	2009-02-27
AU2007211399B2 (en)	2012-09-20
WO2007088277A1 (fr)	2007-08-09
US8288376B2 (en)	2012-10-16
EP1987010A1 (fr)	2008-11-05
JP2009525313A (ja)	2009-07-09
DOP2007000022A (es)	2007-09-15
HK1129670A1 (en)	2009-12-04
CA2637333A1 (fr)	2007-08-09
JO2602B1 (en)	2011-11-01
EA014450B1 (ru)	2010-12-30
US8143248B2 (en)	2012-03-27
TWI401256B (zh)	2013-07-11
CN101379041A (zh)	2009-03-04
IL192648A (en)	2012-06-28
CA2637333C (fr)	2015-12-29
US20120122852A1 (en)	2012-05-17
EP1987010B1 (fr)	2010-04-07
FR2897061B1 (fr)	2010-09-03
SI1987010T1 (sl)	2010-07-30

Publication	Publication Date	Title
JP5136938B2 (ja)	2013-02-06	ベンゾイミダゾール単位を含む三環式ｎ−ヘテロアリール−カルボキサミド誘導体、それらの調製方法およびそれらの治療上の使用
US8354425B2 (en)	2013-01-15	Azabicyclic carboxamide derivatives, preparation thereof and therapeutic use thereof
JP5264773B2 (ja)	2013-08-14	Ｎ−（ヘテロアリール）−１−ヘテロアリール−１ｈ−インドール−２−カルボキサミドの誘導体、これらの調製およびこれらの治療用途
US8394820B2 (en)	2013-03-12	N-azabicyclic carboxamide derivatives, preparation thereof and therapeutic use thereof
US8604050B2 (en)	2013-12-10	Bicyclic derivatives of azabicyclic carboxamides, preparation thereof and therapeutic use thereof
AU2006271518B2 (en)	2012-03-01	N(arylalkyl)-1h-pyrrolopyridine-2-carboxamide derivatives, preparation and therapeutic use thereof
US8420817B2 (en)	2013-04-16	Tricyclic N-heteroaryl-carboxamide derivatives, preparation and therapeutic use thereof
US8044066B2 (en)	2011-10-25	Derivatives of pyrrolopyridine-2-carboxamides, preparation thereof and therapeutic application thereof
MX2008009926A (es)	2008-10-03	Derivados de n-heteroaril-carboxamidas triciclicas que contienen un resto bencimidazol, su preparacion y su aplicacion en terapeutica

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